Talk:Abnormal Development - Illegal Drugs
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Abnormal Development - Cannabis
Abnormal Development - Cocaine
Abnormal Development - Heroin
Abnormal Development - Organic Solvents
Abnormal Development - Methamphetamine
Clin Obstet Gynecol. 2018 Dec 31. doi: 10.1097/GRF.0000000000000418. [Epub ahead of print] Stimulant Use in Pregnancy: An Under-recognized Epidemic Among Pregnant Women. Smid MC1,2,3, Metz TD1, Gordon AJ2,3. Author information Abstract Stimulant use, including cocaine, methamphetamines, ecstasy, and prescription stimulants, in pregnancy is increasingly common. In the United States, stimulants are the second most widely used and abused substances during pregnancy and pregnant women using stimulants in pregnancy are at increased risk of adverse perinatal, neonatal, and childhood outcomes. In this review, we describe the pharmacology, pathophysiology, and epidemiology of stimulants, summarize the maternal and neonatal effects of perinatal stimulant use, and outline treatment options for stimulant use disorders among pregnant women. Development of effective treatment strategies for stimulant use disorders identified among pregnant women are urgently needed.
PMID: 30601144 DOI: 10.1097/GRF.0000000000000418
Coca: The History and Medical Significance of an Ancient Andean Tradition
Emerg Med Int. 2016;2016:4048764. doi: 10.1155/2016/4048764. Epub 2016 Apr 7.
Biondich AS1, Joslin JD1.
Coca leaf products are an integral part of the lives of the Andean peoples from both a cultural and traditional medicine perspective. Coca is also the whole plant from which cocaine is derived. Coca products are thought to be a panacea for health troubles in regions of South America. This review will examine the toxicology of whole coca and will also look at medicinal applications of this plant, past, present, and future. PMID 27144028 PMCID: PMC4838786 DOI: 10.1155/2016/4048764
Prenatal cannabis exposure and infant outcomes: overview of studies
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jul 3;52:45-52. doi: 10.1016/j.pnpbp.2013.09.014. Epub 2013 Sep 27.
Accumulating evidence from both human and preclinical studies indicates maternal substance use during pregnancy can affect fetal development, birth weight and infant outcomes. Thus, the prenatal period can be regarded as an important and potentially sensitive period of development. In this manuscript, an updated overview of studies on prenatal cannabis exposure in humans is presented, including recent studies conducted within the Generation R study. Findings on fetal growth, birth outcomes, early neonatal behavior and infant behavior and cognitive development are discussed in detail. Preclinical evidence and potential mechanisms are described as well, and recommendations for future studies are provided. It is concluded that evidence seems to suggest that fetal development is affected by prenatal maternal cannabis use, while findings on effects on infant behavior or cognition are inconsistent. Beyond infancy, subtle differences may be found in specific cognitive or behavioral outcomes, although replication studies in which pregnant women and their fetuses are exposed to current and probably higher levels of Δ9-tetrahydrocannabinol and novel designs are needed to come to firm conclusions. © 2013. KEYWORDS: Behavior; Fetal growth; Infancy; Prenatal cannabis exposure; Review
A case-control study of maternal periconceptual and pregnancy recreational drug use and fetal malformation using hair analysis
PLoS One. 2014 Oct 31;9(10):e111038. doi: 10.1371/journal.pone.0111038. eCollection 2014.
David AL1, Holloway A1, Thomasson L1, Syngelaki A2, Nicolaides K3, Patel RR4, Sommerlad B5, Wilson A6, Martin W6, Chitty LS7.
Abstract OBJECTIVE: Maternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method. METHODS: In a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period). RESULTS: Women whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78±SD4.79 years, 18-37 vs 29.79±SD6 years, 18-42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95thCI 1.08-4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95thCI 0.18-0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95th CI1.20-10.02, p = 0.01). CONCLUSIONS: We demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age.
Cocaine and its metabolites in the placenta: a systematic review of the literature
Reprod Toxicol. 2012 Jan;33(1):1-14. doi: 10.1016/j.reprotox.2011.10.012. Epub 2011 Nov 6.
De Giovanni N, Marchetti D. Source Institute of Forensic Medicine, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, 00168 Rome, Italy. firstname.lastname@example.org
It is clear that cocaine and cocaine metabolites are present in the placenta and may harm the fetus. The results of the experimental manipulation of cocaine exposure are not reported in the literature in a consistent manner. We conducted a systematic review of selected articles that demonstrated the analytical detection of cocaine and its metabolites in the placenta and that were published from January 1, 1956-June 30, 2011 using Medline, Toxline and Scopus databases. The collected data confirm that the placenta does not act as a barrier to fetal exposure, that cocaine quickly crosses the placenta and that one of the essential roles of the placenta is to metabolize cocaine during pregnancy. Our systematic review summarized the results showing that cocaine, benzoylecgonine and norcocaine are stored in the myometrium and the placental membrane and maintain continuous drug delivery to the amniotic fluid (and to the fetus) probably via diffusion. Copyright © 2011 Elsevier Inc. All rights reserved.
The Use of Narcotics and Street Drugs During Pregnancy
Clin Obstet Gynecol. 2013 Jan 9. [Epub ahead of print]
Lindsay MK, Burnett E. Source Department of Gynecology and Obstetrics, Emory University, Atlanta, GA.
All prenatal care providers should offer routine voluntary substance use screening to all patients. Parturients who screen positive for illicit substances require a multidisciplinary team approach to drug rehabilitation and prenatal care. This review will examine the pharmacological properties and the neonatal consequences of the use of opioids and amphetamines. Substance-abusing parturients typically abuse multiple substances simultaneously and have other comorbidities including psychosocial instability and mental illness. These comorbidities must be effectively addressed to achieve optimal health outcomes for both mother and infant. PMID 23314719
Cocaine use during pregnancy assessed by hair analysis in a Canary Islands cohort
BMC Pregnancy Childbirth. 2012 Jan 9;12:2.
Joya X, Gomez-Culebras M, Callejón A, Friguls B, Puig C, Ortigosa S, Morini L, Garcia-Algar O, Vall O. Source Unitat de Recerca Infància i Entorn, Institut de Recerca Parc de Salut Mar, Barcelona, Spain. email@example.com Abstract BACKGROUND: Drug use during pregnancy is difficult to ascertain, and maternal reports are likely to be inaccurate. The aim of this study was to estimate the prevalence of illicit drug use among pregnant women by using maternal hair analysis. METHODS: A toxicological analysis of hair was used to detect chronic recreational drug use during pregnancy. In 2007, 347 mother-infant dyads were included from the Hospital La Candelaria, Santa Cruz de Tenerife, Canary Islands (Spain). Data on socioeconomic characteristics and on substance misuse during pregnancy were collected using a structured questionnaire. Drugs of abuse: opiates, cocaine, cannabinoids and amphetamines were detected in maternal hair by immunoassay followed by gas chromatography-mass spectrometry for confirmation and quantitation. RESULTS: Hair analysis revealed 2.6% positivity for cocaine and its metabolites. Use of cocaine during pregnancy was associated with unusual behaviour with potentially harmful effects on the baby. CONCLUSIONS: The results of the study demonstrate significant cocaine use by pregnant women in Canary Islands. The data should be used for the purpose of preventive health and policy strategies aimed to detect and possibly to avoid in the future prenatal exposure to drugs of abuse.
Consequences of prenatal substance use
Int J Adolesc Med Health. 2011 Nov 29;24(2):105-12. doi: 10.1515/ijamh.2012.016.
Sithisarn T, Granger DT, Bada HS. Source Department of Pediatrics, University of Kentucky College of Medicine, Lexingon, KY 40536, USA. Abstract BACKGROUND: Prenatal substance use is a major public health problem and a social morbidity, with consequences on the drug user and the offspring. OBJECTIVE: This review focuses on the child and adolescent outcomes following in utero drug exposure. METHODS: Studies on the effects of specific substances, legal and illegal; i.e., tobacco or nicotine, alcohol, marijuana, cocaine, opiates, and methamphetamine were evaluated and analyzed. RESULTS: In general, manifestations of prenatal exposure to legal and illegal substances include varying deficits in birth anthropometric measurements, mild-to-moderate transient neurobehavioral alterations in infancy and long-term behavioral problems noted from early childhood to adolescence. Severity of expression of behavioral problems is influenced by environmental factors. Further, behavioral alterations following in utero drug exposure often exist with mental health co-morbidities. CONCLUSION: Because of the long-term consequences of prenatal drug exposure on child and adolescent mental health, health providers need to promote substance use prevention, screen for exposure effects and provide or refer affected youths for intervention services. Preventive measures and treatment should consider other factors that may further increase the risk of psychopathology in the exposed children. PMID 22909919
Comprehensive treatment program for pregnant substance users in a family medicine clinic
Can Fam Physician. 2011 Nov;57(11):e430-5.
Ordean A, Kahan M. Source Toronto Centre for Substance Use in Pregnancy, St Joseph's Health Centre, Toronto, ON. firstname.lastname@example.org Abstract PROBLEM BEING ADDRESSED: Substance use during pregnancy is a substantial public health problem and a risk factor for poor neonatal outcomes. Prenatal care is often provided in high-risk pregnancy units, separate from addiction treatment. OBJECTIVE OF PROGRAM: To provide comprehensive prenatal care and addiction treatment in a family medicine setting. DESCRIPTION OF PROGRAM: The Toronto Centre for Substance Use in Pregnancy (T-CUP) is a family medicine-based program in a large urban city in Ontario. The T-CUP program comprises an interdisciplinary team using a one-stop access model to provide comprehensive services for pregnant women with a history of alcohol or drug abuse, including prenatal and postnatal medical care, addiction counseling, and assistance with complex psychosocial needs. EVALUATION: A retrospective chart review was performed, including charts for 121 women who received care at T-CUP from August 2000 to January 2006. Women demonstrated a high compliance rate with prenatal care attendance. Most women reported reduction in a variety of drug use categories. Significant differences were found especially among women who presented earlier in their pregnancies (P < .05). As a result, neonatal outcomes were satisfactory and approximately 75% of newborns were discharged home in the care of their mothers. CONCLUSION: Pregnant substance-using women have positive maternal and infant health outcomes when they receive comprehensive care in a family medicine setting. PMID 22084472
Specificity of prenatal cocaine exposure effects on cortical interneurons is independent from dopamine D1 receptor co-localization
J Chem Neuroanat. 2010 Jul;39(4):228-34. Epub 2010 Jan 18.
Thompson BL, Stanwood GD, Levitt P. Source Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States. email@example.com <firstname.lastname@example.org>
Gestational cocaine exposure in a rabbit model leads to a persistent increase in parvalbumin immunoreactive cells and processes, reduces dopamine D1 receptor coupling to Gsalpha by means of improper trafficking of the receptor, changes pyramidal neuron morphology, and disrupts cognitive function. Here, experiments investigated whether changes in parvalbumin neurons were specific, or extended to other subpopulations of interneurons. Additionally, we examined dopamine D1 receptor expression patterns and its overlap with specific interneuron populations in the rabbit prefrontal cortex as a possible correlate for alterations in interneuron development following prenatal cocaine exposure. Analysis of calbindin and calretinin interneuron subtypes revealed that they did not exhibit any differences in cell number or process development. Thus, specific consequences of prenatal cocaine in the rabbit appear to be limited to parvalbumin-positive interneurons. Dopamine D1 receptor expression did not correlate with the selective effects of cocaine exposure, however, as both parvalbumin and calbindin cell types expressed the receptor. The findings suggest that additional, unique properties of parvalbumin neurons contribute to their developmental sensitivity to in utero cocaine exposure.
Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand
Neurotoxicol Teratol. 2010 Jul 6.
Lagasse LL, Wouldes T, Newman E, Smith LM, Shah RZ, Derauf C, Huestis MA, Arria AM, Grotta SD, Wilcox T, Lester BM.
Center for the Study of Children at Risk, Warren Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI, USA. Abstract BACKGROUND: Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants.
DESIGN: The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte.
RESULTS: MA exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress.
CONCLUSION: Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress.
Copyright © 2010. Published by Elsevier Inc. All rights reserved.
Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor-based brain morphometry and discriminant analysis
J Neurosci. 2010 Mar 17;30(11):3876-85.
Sowell ER, Leow AD, Bookheimer SY, Smith LM, O'Connor MJ, Kan E, Rosso C, Houston S, Dinov ID, Thompson PM.
Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA. email@example.com Abstract Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5-15 years), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally and in right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and, within the MAA group, a negative correlation between full-scale intelligence quotient (FSIQ) scores and caudate volume was observed. Limbic structures, including the anterior and posterior cingulate, the inferior frontal gyrus (IFG), and ventral and lateral temporal lobes bilaterally, were increased in volume in both exposure groups. Furthermore, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure and that more severe striatal damage is associated with more severe cognitive deficit.
Fetal effects of psychoactive drugs
Clin Perinatol. 2009 Sep;36(3):595-619.
Salisbury AL, Ponder KL, Padbury JF, Lester BM.
Department of Pediatrics, Brown Center for the Study of Children at Risk, Women and Infants Hospital of Rhode Island, 101 Dudley Street, Providence, RI 02905, USA. firstname.lastname@example.org Abstract Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.
Vulnerability to (+)-methamphetamine effects and the relationship to drug disposition in pregnant rats during chronic infusion
Toxicol Sci. 2009 Sep;111(1):27-36. Epub 2009 Jun 10.
White SJ, Laurenzana EM, Gentry WB, Hendrickson HP, Williams DK, Ward KW, Owens SM.
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. Abstract Chronic (+)-methamphetamine (METH) use during pregnancy increases the health risk for both mother and fetus. To provide insights into these risks, the relationship between changes in METH disposition and METH-induced pharmacological effects were studied in Sprague-Dawley rat dams and litters. Timed-pregnant rats (n = 5-6) were given saline or METH (5.6-17.8 mg/kg/day) by continuous sc infusion from gestational day (GD) 7 (before organogenesis) until GD21 (0-2 days before delivery). By GD11, all rats in the 17.8-mg/kg/day group died or were sacrificed for humane reasons. There were significant (p < 0.05) dose- and gestational time-dependent decreases in maternal body weight in the 10- to 13.2-mg/kg/day groups, which slowly recovered to near normal by GD21. Continued METH dosing in the surviving groups did not affect the mean pups/litter weight at the end of the experiment on GD21. While maternal and fetal METH and (+)-amphetamine serum concentrations were similar on GD21, brain concentrations were significantly greater in the dams (p < 0.05). Importantly, brain-to-serum ratios in the dams were 9:1 and 3:1 in the pups. METH systemic clearance (Cl(S)) in dams significantly (p < 0.05) decreased from 52 +/- 14 ml/min/kg on GD10 to 28 +/- 6 ml/min/kg on GD21 in all dose groups, indicating late-gestational stage reductions in METH Cl(S). Overall, these findings suggest that there were two periods of increased susceptibility for dams and fetuses during chronic METH treatment. First was the period after the start of METH dosing in which neuroadaptation and tolerance to METH occurs in the adult. The second was at the end of pregnancy when METH clearance was significantly reduced.
Neuroimaging of children following prenatal drug exposure
Semin Cell Dev Biol. 2009 Jun;20(4):441-54. Epub 2009 Mar 13. Derauf C, Kekatpure M, Neyzi N, Lester B, Kosofsky B.
John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. Abstract Recent advances in MR-based brain imaging methods have provided unprecedented capabilities to visualize the brain. Application of these methods has allowed identification of brain structures and patterns of functional activation altered in offspring of mothers who used licit (e.g., alcohol and tobacco) and illicit (e.g., cocaine, methamphetamine, and marijuana) drugs during pregnancy. Here we review that literature, which though somewhat limited by the complexities of separating the specific effects of each drug from other confounding variables, points to sets of interconnected brain structures as being altered following prenatal exposure to drugs of abuse. In particular, dopamine-rich cortical (e.g., frontal cortex) and subcortical (e.g., basal ganglia) fetal brain structures show evidence of vulnerability to intrauterine drug exposure suggesting that during brain development drugs of abuse share a specific profile of developmental neurotoxicity. Such brain malformations may shed light on mechanisms underlying prenatal drug-induced brain injury, may serve as bio-markers of significant intrauterine drug exposure, and may additionally be predictors of subsequent neuro-developmental compromise. Wider clinical use of these research-based non-invasive methods will allow for improved diagnosis and allocation of therapeutic resources for affected infants, children, and young adults.
Maternal depression and neurobehavior in newborns prenatally exposed to methamphetamine
Neurotoxicol Teratol. 2009 May-Jun;31(3):177-82. Epub 2008 Dec 3 Paz MS, Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A, Huestis M, Haning W, Strauss A, Della Grotta S, Liu J, Lester BM.
Los Angeles Biomedical Institute at Harbor-UCLA Medical Center and David Geffen School of Medicine at UCLA, USA. Abstract BACKGROUND: The effects of maternal depression on neonatal neurodevelopment in MA exposed neonates have not been well characterized.
OBJECTIVE: To determine the neurobehavioral effects of maternal depressive symptoms on neonates exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS).
DESIGN: The purpose of the IDEAL study is to determine the effects of prenatal MA exposure on child outcome. IDEAL screened 13,808 subjects, 1632 were eligible and consented and 176 mothers were enrolled. Only biological mothers with custody of their child at the one-month visit (n=50 MA; n=86 comparison) had the Addiction Severity Index (ASI) administered. The NNNS was administered to the neonate by an examiner blinded to MA exposure within the first five days of life. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS outcomes, with and without covariates. Significance was accepted at p<.05.
RESULTS: After adjusting for covariates, regardless of exposure status, maternal depressive symptoms were associated with lower handling and arousal scores, elevated physiological stress scores and an increased incidence of hypotonicity. When adjusting for covariates, MA exposure was associated with lower arousal and higher lethargy scores.
CONCLUSIONS: Maternal depressive symptoms are associated with neurodevelopmental patterns of decreased arousal and increased stress. Prenatal MA exposure combined with maternal depression was not associated with any additional neonatal neurodevelopmental differences.